A new study just published in the New England Journal of Medicine of over 31,000 people found that those taking the highest levels of Vitamin D (over 800IU which by many standards is not high at all) had a 30% reduction in him and 14% reduction in non-vertebral fractures. There was no significant reduction in people taking less than 800IU per day.
In a meta-analysis, oral doses of at least 800 IU were associated with
reductions in the risk of both hip and nonvertebral fractures, according
to Heike Bischoff-Ferrari, MD, DrPH, of University Hospital in Zurich,
The analysis differs from previous studies and other meta-analyses in
that it looked at how much vitamin D participants actually took, rather
than what dose they were assigned to take, Bischoff-Ferrari and
colleagues reported in the July 5 issue of the New England Journal of
Fractures are common in older people and one strategy to prevent them
might be vitamin D supplements, the researchers noted, but studies of
the issue have been inconsistent. To try to clarify the matter, they
looked for all controlled studies of oral vitamin D, with or without
calcium, among people 65 and older.
They included 12 studies and had participant-level data on 30,011
The primary end points were the risks of hip fracture and any
nonvertebral fracture, and the primary analyses compared the actual
intake of vitamin D supplementation, in quartiles, to the controls, with
actual intake calculated as the assigned dose plus any additional
supplemental dose, adjusted for adherence.
The study design is important, because it takes into account the biology
of vitamin supplementation, according to Robert Heaney, MD, of the
Creighton University Medical Center in Omaha, Neb.
In an accompanying editorial in the journal, Heaney argued that the
inconsistent outcomes of earlier work might be the result of an
overfocus in meta-analyses on the methods used in individual trials.
“The question of how much vitamin D is enough is likely to remain
muddled as long as meta-analyses focus on trial methodology rather than
on biology,” he argued.
But Heaney noted that the results of the current meta-analysis are in
accordance with recommendations of the Endocrine Society. “It would
appear to be prudent, and probably helpful as well, to ensure an intake
at the upper end of the range” that the researchers found effective.
Bischoff-Ferrari and colleagues found that, in an intention-to-treat
analysis, there was a nonsignificant 10% reduction in the risk of hip
fracture and a significant (at P=0.03) 7% reduction in the risk of
On the other hand, when they took into account actual vitamin D intake,
they found a 30% reduction in the risk of hip fracture but only for
those in the highest quartile of intake – 792 to 2,000 IU a day.
The relative risk in that group, compared with controls, was 0.70, with
a 95% confidence interval from 0.58 to 0.86, and was significant at P<0.001.
They also found a 14% reduction in the risk of any nonvertebral
fracture, but again only in the highest quartile. The relative risk was
0.86, with a 95% confidence interval from 0.66 to 0.96, and was
significant at P=0.007.
A sensitivity analysis, not including any outside supplements, had
similar results, they reported.
Heaney commented that the benefits of supplements might be affected by
baseline levels of vitamin D but noted that such information has not
been routinely collected in trials of the substance.
Indeed, baseline levels of hydroxyvitamin D were only available for
4,383 participants, Bischoff-Ferrari and colleagues reported. Despite
that, the results among those participants were similar to those in the
whole group, they found.
In addition to the absence of baseline hydroxyvitamin D levels, other
study limitations included inability to separate calcium and vitamin D
intake as those receiving high doses of vitamin D were all taking
calcium and lack of trial level data for two of the 14 included trials.